Cell-Cell Interaction in Vitro: Studied by Density Separation of Colony-forming, Stimulating, and Inhibiting Cells From Human Bone Marrow

Cell-cell interaction in vitro was studied by separating normal human bone marrow cells into fractions on the basis of their buoyant density in a linear gradient of bovine serum albumin and by assaying the colony forming ability of marrow fractions and combinations of marrow fractions in methylcellulose medium without an added extrinsic source of colony-stimulating factor. In this culture system unfractionated marrow cells seldom formed colonies, but colonies grew from the low-density fractions, suggesting that an inhibitor had been removed by cell fractionation. When cells from the low-density fraction were mixed with the cells from the middensity and highdensity fractions, stimulation and inhibition of colony size respectively were observed. These observations suggest that cell-cell interaction may play a role in regulation of granulopoiesis in vitro and suggests an approach to the investigation of granulopoiesis in disease.